{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:10:06Z","timestamp":1790021406907,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2016,5,29]],"date-time":"2016-05-29T00:00:00Z","timestamp":1464480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Duchenne Alliance","award":["100065 and 100071"],"award-info":[{"award-number":["100065 and 100071"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2016,10,15]]},"abstract":"<jats:sec><jats:title>Key point<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>PGC\u20101\u03b1 pathway activation has been shown to decrease disease severity and can be driven by quercetin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Oral quercetin supplementation protected respiratory function for 4\u20136 months during a 12 month dosing regimen.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This transient protection was probably due to a failure to sustain elevated SIRT1 activity and downstream PGC\u20101\u03b1 signalling.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Quercetin supplementation may be a beneficial treatment as part of a cocktail provided continued SIRT1 activity elevation is achieved.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) impacts 1\u00a0:\u00a03500 boys and leads to muscle dysfunction culminating in death due to respiratory or cardiac failure. There is an urgent need for effective therapies with the potential for immediate application for this patient population. Quercetin, a flavonoid with an outstanding safety profile, may provide therapeutic relief to DMD patients as the wait for additional therapies continues. This study evaluated the capacity of orally administered quercetin (0.2%) in 2\u00a0month old mdx mice to improve respiratory function and end\u2010point functional and histological outcomes in the diaphragm following 12\u00a0months of treatment. Respiratory function was protected for the first 4\u20136\u00a0months of treatment but appeared to become insensitive to quercetin thereafter. Consistent with this, end\u2010point functional measures were decreased and histopathological measures were more severe in dystrophic muscle compared to C57 and similar between control\u2010fed and quercetin\u2010fed mdx mice. To better understand the transient nature of improved respiratory function, we measured PGC\u20101\u03b1 pathway activity, which is suggested to be up\u2010regulated by quercetin supplementation. This pathway was largely suppressed in dystrophic muscle compared to healthy muscle, and at the 14\u00a0month time point dietary quercetin enrichment did not increase expression of downstream effectors. These data support the efficacy of quercetin as an intervention for DMD in skeletal muscle, and also indicate the development of age\u2010dependent quercetin insensitivity when continued supplementation fails to drive the PGC\u20101\u03b1 pathway. Continued study is needed to determine if this is related to disease severity, age or other factors.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272057","type":"journal-article","created":{"date-parts":[[2016,4,20]],"date-time":"2016-04-20T12:02:55Z","timestamp":1461153775000},"page":"6037-6053","source":"Crossref","is-referenced-by-count":24,"title":["Oral quercetin administration transiently protects respiratory function in dystrophin\u2010deficient mice"],"prefix":"10.1113","volume":"594","author":[{"given":"Joshua T.","family":"Selsby","sequence":"first","affiliation":[{"name":"Department of Animal Science Iowa State University  Ames IA 50011 USA"},{"name":"School of Kinesiology Auburn University  Auburn AL 36849 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Ballmann","sequence":"additional","affiliation":[{"name":"Department of Animal Science Iowa State University  Ames IA 50011 USA"},{"name":"School of Kinesiology Auburn University  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